The general objective of this project is to determine whether cyclic 3',5'-AMP (cAMP) (or another cyclic nucleotide) participates in the action of sex steroid hormones at the nuclear locus. The data presently available in this field are contradictory and confusing. To resolve this issue, a series of investigations have been undertaken to provide direct evidence for or against this idea. As a basis for experimental investigation, a working hypothesis was developed that the initiation of selective RNA synthesis associated with steroid action, requires the cooperative interaction of both receptor- steroid complexes and cAMP associated with binding protein (perhaps cAMP dependent protein kinase). Four lines of experimental investigation are projected for 1973, involving androgen action in the rat ventral prostate: (1) To determine whether steroid hormones (whether "free" or complexed with "receptor"), stimulate adenyl cyclase activities in nuclei or in other subcellular fractions of prostate tissue homogenates. (2) To study the effects of testosterone and other hormones upon cAMP formation in the intact cells of prostate tissue. (3) The effects of cAMP, cAMP-dependent protein kinase, steroids and androgen receptors (from the cytosol of prostate tissue) will be studied alone and in combination on RNA synthesis and phosphorylation of nuclear proteins in isolated nuclei of normal and castrate rats. These studies should provide direct evidence on the relationship of phosphorylation of nuclear proteins (histones and acidic proteins) to regulation of RNA synthesis.